There are two specific aims of this project: (1) to increase the number of genes mapped on human chromosomes by extensive family studies utilizing rare chromosome variants and common chromosome polymorphisms. Loci to be linked to the identifiable homologues include the HL-A system in our laboratory and 25 red cell, serum and saliva markers in the laboratory of Dr. Lovrien; (2) to determine the parental origin of the extra chromosome in free trisomy 2l Down's syndrome patients; further, to determine if the error is a first meiotic error or after meiosis I. New chromosome banding techniques have permitted intra-pair chromosome identification; these differences between homologues appear to be heritable. By finding which parent contributed two chromosomes 21 we will know the parental origin; two different chromosomes 21 from a parent should indicate a first meiotic error, while two identical, a second meiotic or post-zygotic mitotic error. This grant proposal is a coordinate one with those being submitted by Drs. Everett Lovrien and Frederick Hecht. Fracilities, equipment and projects are shared; our overall aim, to further human autosome mapping, is shared. Each has specific background for a portion of the aim: Dr. E. Lovrien, Polymorphism of autosomal genes, including dominant traits; Dr. Frederick Hecht, extensive cytogenetic experience and cell hybridization experience; Dr. Ellen Magenis, cytogenetic and family study experience. Part 2 will be a coordinate but not dependent effort with that of Dr. Irvin Emanuel and Lowell Sever, Jr., utilizing in part the same Down's syndrome populaion. Their research proposal is entitled: Maternal Biologic Aging and Down's Syndrome.